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Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats
Author(s) -
Musicki B.,
Hannan J. L.,
Lagoda G.,
Bivalacqua T. J.,
Burnett A. L.
Publication year - 2016
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12218
Subject(s) - enos , endothelial dysfunction , medicine , erectile dysfunction , endocrinology , vasodilation , oxidative stress , nadph oxidase , penis , endothelium , nitric oxide synthase , nitric oxide , anatomy
Summary Men with type 2 diabetes mellitus (T2 DM ) and erectile dysfunction ( ED ) have greater risk of cardiovascular events than T2 DM men without ED , suggesting ED as a predictor of cardiovascular events in diabetic men. However, molecular mechanisms underlying endothelial dysfunction in the diabetic penis explaining these clinical observations are not known. We evaluated whether the temporal relationship between ED and endothelial dysfunction in the systemic vasculature in T2 DM involves earlier redox imbalance and endothelial nitric oxidase synthase ( eNOS ) dysfunction in the penis than in the systemic vasculature, such as the carotid artery. Rats were rendered T2 DM by high‐fat diet for 2 weeks, followed by an injection with low‐dose streptozotocin. After 3 weeks, erectile function (intracavernosal pressure) was measured and penes and carotid arteries were collected for molecular analyses of eNOS uncoupling, protein S‐glutathionylation, oxidative stress (4‐hydroxy‐2‐nonenal, 4‐ HNE ), protein expression of NADPH oxidase subunit gp91 phox , endothelium‐dependent vasodilation in the carotid artery, and non‐adrenergic, non‐cholinergic ( NANC )‐mediated cavernosal relaxation. Erectile response to electrical stimulation of the cavernous nerve and NANC ‐mediated cavernosal relaxation was decreased ( p < 0.05), while relaxation of the carotid artery to acetylcholine was not impaired in T2 DM rats. eNOS monomerization, protein expressions of 4‐ HNE and gp91 phox , and protein S‐glutathionylation, were increased ( p < 0.05) in the penis, but not in the carotid artery, of T2 DM compared to non‐diabetic rats. In conclusion, redox imbalance, increased oxidative stress by NADPH oxidase, and eNOS uncoupling, occur early in T2 DM in the penis, but not in the carotid artery. These molecular changes contribute to T2 DM ED , while vascular function in the systemic vasculature remains preserved.